Linoleic acid metabolite drives severe asthma by causing airway epithelial injury

Mabalirajan, Ulaganathan; Rehman, Rakhshinda; Ahmad, Tanveer; Kumar, Sarvesh; Singh, Suchita; Leishangthem, Geeta Devi; Aich, Jyotirmoi; Kumar, Manish; Khanna, Kritika; Singh, Vijay Pal; Dinda, Amit Kumar; Biswal, Shyam; Agrawal, Anurag; Ghosh, Balaram

doi:10.1038/srep01349

Cited by 96 publications

(104 citation statements)

References 47 publications

(76 reference statements)

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“…On day 110, AHR was estimated in all mice as described earlier [16], followed by euthanasia to collect bronchoalveolar lavage fluid, blood and lung samples [17,18]. Blood was centrifuged at 1,000 g for 30 min to collect sera.…”

Section: Methodsmentioning

confidence: 99%

“…Blood was centrifuged at 1,000 g for 30 min to collect sera. After measuring lung function, the mice were euthanized and the lungs were fixed with 10% formalin, processed to obtain tissue blocks [16]. Lung tissue sections were sliced at 4-5 μm and then stained with hematoxylin and eosin (HE), periodic acid-Schiff (PAS) and Masson's trichrome (MT) for the assessment of inflammatory changes, goblet cell metaplasia and subepithelial fibrosis, respectively.…”

Section: Methodsmentioning

confidence: 99%

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Parabromophenacyl Bromide Inhibits Subepithelial Fibrosis by Reducing TGF-β<sub>1</sub> in a Chronic Mouse Model of Allergic Asthma

Ram

Mabalirajan²,

Jaiswal³

et al. 2015

Int Arch Allergy Immunol

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Background: Our previous study showed that parabromophenacyl bromide (PBPB) inhibits the features of allergic airway inflammation and airway hyperresponsiveness (AHR). However, its effect on airway remodeling, e.g. subepithelial ﬁbrosis in a chronic allergic asthma model, was not investigated. We examined this issue in this study. Methods: PBPB was administered to mice with an induced chronic asthmatic condition. AHR was estimated at the end of the experiment, followed by euthanasia. Lung sections were stained with hematoxylin and eosin, periodic acid-Schiff and Masson's trichrome to determine airway inflammation, goblet cell metaplasia and subepithelial fibrosis, respectively. Transforming growth factor-β₁ (TGF-β₁) was estimated in lung homogenates. To determine the effect of PBPB on smooth-muscle hyperplasia, immunohistochemistry against α-smooth-muscle actin was performed on the lung sections. Results: Chronic ovalbumin challenges in a mouse model of allergic asthma caused significant subepithelial ﬁbrosis and elevated TGF-β₁, along with significant AHR. PBPB attenuated subepithelial ﬁbrosis with a reduction of lung TGF-β₁, airway inflammation and AHR without affecting goblet cell metaplasia. It also attenuated smooth-muscle hyperplasia with a reduction in the expression of α-smooth-muscle actin in the lungs. Conclusion: Our findings indicate that PBPB attenuates some crucial features of airway remodeling such as subepithelial ﬁbrosis and smooth-muscle hyperplasia. These data suggest that PBPB could therefore be a therapeutic drug for chronic asthma.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Parabromophenacyl Bromide Inhibits Subepithelial Fibrosis by Reducing TGF-β<sub>1</sub> in a Chronic Mouse Model of Allergic Asthma

Ram

Mabalirajan²,

Jaiswal³

et al. 2015

Int Arch Allergy Immunol

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“…hydroperoxy-and hydroxy-fatty acids), i.e. independent 325 of n-3 LCPUFA status [26][27][28]. It is therefore possible that low n-6 LA diets may be 326 associated with clinical benefits in spite of relatively modest effects on n-3 LCPUFA status.…”

mentioning

confidence: 99%

A low omega-6 polyunsaturated fatty acid (n-6 PUFA) diet increases omega-3 (n-3) long chain PUFA status in plasma phospholipids in humans

Wood

Lau

Mantzioris

et al. 2014

Prostaglandins, Leukotrienes and Essential Fatty Acids

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A low omega-6 polyunsaturated fatty acid (n-6 PUFA) diet increases omega-3 (n-3) long chain PUFA status in plasma phospholipids in humans Prostaglandins, Leukotrienes and Essential Fatty Acids, 2014; 90(4) Please note: Cell Press, The Lancet, and some society-owned titles have different preprint policies. Information on these is available on the journal homepage.  Preprints should not be added to or enhanced in any way in order to appear more like, or to substitute for, the final versions of articles. August 20151 A low omega-6 polyunsaturated fatty acid (n-6 PUFA) diet increases omega-3 (n-3) long unchanged. LA and total n-6 PUFA content of plasma and erythrocyte phospholipids were 39 significantly reduced after the low LA diet phase (P<0.001). The n-3 LCPUFA content was 40 significantly increased in plasma phospholipids after the low LA diet compared to baseline 41 (6.22% vs 5.53%, P<0.001). These data demonstrate that reducing LA intake for 4 weeks 42 increases n-3 LCPUFA status in humans in the absence of increased n-3 LCPUFA intake.

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“…play a critical role in the development of respiratory diseases including asthma, chronic obstructive pulmonary diseases, allergic rhinitis, and others (9). Therefore, some researchers believed that the polymorphism of the TRPV gene may be associated with the hereditary susceptibility of asthma (10).…”

Section: Discussionmentioning

confidence: 99%

Preliminary study on pathogenesis of bronchial asthma in children

Ren

Xing

et al. 2015

Pediatr Res

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Background:The etiology and pathogenesis of bronchial asthma remain unclear. This study is to investigate the risk factors related to bronchial asthma onset in children from genetics and immunology and preliminarily reveal the pathogenesis of bronchial asthma in children. Methods: Real-time quantitative PCR was adopted to detect the expression level of TRPV1 gene and mRNA and enzymelinked immunosorbent assay method to the total immunoglobulin E level and levels of IL-4, IL-5, and IFN-γ in serum in peripheral venous blood for children in two groups. Logistic regression analysis was applied to analyze the most essential factors inducing bronchial asthma in children. results: The mRNA level of TRPV1 in peripheral blood in the case group was higher than that in the control group (P < 0.01). The levels of IL-4, IL-5, and eosinophils in serum in the case group were markedly higher than those in the control group (P < 0.01), while IFN-γ level in the case group was lower than that in the control group (P < 0.01). The results of logistic regression analysis indicated that TRPV1 expression level, IL-4 level, and rs4790522 site mutation were the main risk factors inducing bronchial asthma in children. conclusion: The levels of TRPV1 gene expression and Th1/ Th2 cytokines have a close relationship with asthma onset in children, which provides theoretical evidences for molecular targeted treatment in children with bronchial asthma. Bronchial asthma is a worldwide high-incidence disease. With the highest morbidity and gradually rising trend, it is also the most common chronic respiratory disease in childhood (1). Asthma not only does harm to children's physical and mental health, but also results in a heavy burden to patients' family and society (2). Currently, it has been verified by some studies that asthma is induced by the joint effect of multifactors including immunity, environment, and inheritance and so on (3,4). However, the etiology and pathogenesis of the disease remain unclear. Therefore, it is of great significance for the patients and society to study the etiology and pathological mechanism of asthma.The study of asthma candidate genes demonstrates that the characteristics of gene polymorphism for candidate genes are related to the susceptibility and severity of asthma in children, but still there exist some significant ethnic differences(5). Therefore, the study on the differences of asthma in different races and regions is helpful to early diagnosis, prevention, and treatment of it. In recent years, with the deep understanding of the pathogenesis of bronchial asthma respiratory inflammation, the signal regulatory effect of transient receptor potential cation channel, subfamily V, member 1 (TRPV1) gene on asthma also becomes a research focus. TRPV1, as a V subfamily (TRPV1-TRPV6) member in nonselective cation channel superfamily, shows a relatively extensive expression in mammal respiratory system. Studies have indicated that TRPV1 distributes in respiratory tract and coexists with P substance in the trachea epi...

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Linoleic acid metabolite drives severe asthma by causing airway epithelial injury

Cited by 96 publications

References 47 publications

Parabromophenacyl Bromide Inhibits Subepithelial Fibrosis by Reducing TGF-β<sub>1</sub> in a Chronic Mouse Model of Allergic Asthma

Parabromophenacyl Bromide Inhibits Subepithelial Fibrosis by Reducing TGF-β<sub>1</sub> in a Chronic Mouse Model of Allergic Asthma

A low omega-6 polyunsaturated fatty acid (n-6 PUFA) diet increases omega-3 (n-3) long chain PUFA status in plasma phospholipids in humans

Preliminary study on pathogenesis of bronchial asthma in children

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